Shapiro E, Krivit W, Lockman L, Jambaqué I, Peters C, Cowan M, Harris R, Blanche S, Bordigoni P, Loes D, Ziegler R, Crittenden M, Ris D, Berg B, Cox C, Moser H, Fischer A, Aubourg P
Division of Paediatric Neurology, University of Minnesota, Minneapolis 55455, USA.
Lancet. 2000 Aug 26;356(9231):713-8. doi: 10.1016/S0140-6736(00)02629-5.
The childhood-onset cerebral form of X-linked adrenoleukodystrophy, a demyelinating disorder of the central nervous system, leads to a vegetative state and death within 3-5 years once clinical symptoms are detectable. The hypothesis to be tested was whether bone-marrow transplantation can over an extended period of time halt the inexorable progressive demyelination and neurological deterioration.
12 patients with childhood onset of cerebral X-linked adrenoleukodystrophy have been followed for 5-10 years after bone-marrow transplantation. Magnetic resonance imaging (MRI), neurological, neuropsychological, electrophysiological, and plasma very-long-chain fatty acid (VLCFA) measurements were used to evaluate the effect of this treatment.
MRI showed complete reversal of abnormalities in two patients and improvement in one. One patient showed no change from baseline to last follow-up. All eight patients who showed an initial period of continued demyelination stabilised and remained unchanged thereafter. Motor function remained normal or improved after bone-marrow transplantation in ten patients. Verbal intelligence remained within the normal range for 11 patients. Performance (non-verbal) abilities were improved or were stable in seven patients. Decline in performance abilities followed by stability occurred in five patients. Plasma VLCFA concentrations decreased by 55% and remained slightly above the upper limits of normal.
5-10-year follow-up of 12 patients with childhood-onset cerebral X-linked adrenoleukodystrophy shows the long-term beneficial effect of bone marrow transplantation when the procedure is done at an early stage of the disease.
X连锁肾上腺脑白质营养不良的儿童期起病脑型，是一种中枢神经系统脱髓鞘疾病，一旦出现临床症状，会在3至5年内导致植物人状态并死亡。有待检验的假设是骨髓移植能否在较长时间内阻止不可避免的进行性脱髓鞘和神经功能恶化。
12例儿童期起病的脑型X连锁肾上腺脑白质营养不良患者在接受骨髓移植后接受了5至10年的随访。采用磁共振成像（MRI）、神经学、神经心理学、电生理学以及血浆极长链脂肪酸（VLCFA）测量来评估这种治疗的效果。
MRI显示两名患者的异常完全逆转，一名患者有所改善。一名患者从基线到最后一次随访无变化。所有8例最初表现为持续脱髓鞘的患者病情稳定，此后保持不变。10例患者骨髓移植后运动功能保持正常或有所改善。11例患者的语言智力保持在正常范围内。7例患者的操作（非语言）能力有所提高或保持稳定。5例患者操作能力下降后又保持稳定。血浆VLCFA浓度下降了55%，仍略高于正常上限。
对12例儿童期起病的脑型X连锁肾上腺脑白质营养不良患者进行5至10年的随访显示，在疾病早期进行骨髓移植具有长期有益效果。
